In the past ten years, collagen has been found to be distributed in structurally distinct types in various tissues. Biochemical techniques have also been devised which allow these collagens to be solubilized from tissues in a highly purified native state. Thus, by use of these collagen preparations, it is now possible to test the hypothesis that type-specific immune responses to collagen may play a role in initiating or perpetuating inflammation occurring in the connective tissue diseases. The major hypothesis of this proposal is that, since a unique type of collagen (type II) is found in cartilage, a type-specific immune reaction to this collagen could explain the predilection of inflammatory arthritides, such as rheumatoid arthritis, to involve diarthrodial joints. We have recently provided direct support for this suggestion by delineating a unique animal model of autoimmunity: type II collagen-induced arthritis in rats. By achieving adoptive transfer of the disease, we have directly implicated immunologic hypersensitivity to type II collagen in the causation of this arthritis. This project proposes to continue our investigations into the role that humoral and cellular sensitivity to collagen may have in the pathogenesis of: 1) Type II collagen-induced arthritis and 2) other connective tissue diseases.